Intellia Therapeutics has temporarily paused patient dosing and screening in its Phase 3 MAGNITUDE and MAGNITUDE-2 trials for Nex-Z, a CRISPR-based therapy for transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN). This suspension follows a serious security incident involving a participant.
Protocol halted due to grade 4 liver toxicity
According to the company, a patient participating in the MAGNITUDE trial on September 30 had a grade 4 liver transaminase increase and increased total bilirubin, reported on October 24. This event met protocol criteria to stop the study. The patient has been admitted to the hospital and is being treated under strict observation.
The company prioritizes patient safety
“Consistent with our commitment to patient safety, we have taken immediate action to temporarily pause enrollment in MAGNITUDE and MAGNITUDE-2 as we investigate this recent incident,” CEO John Leonard, MD, said in a statement. “As we remain focused on ensuring the health of this patient, we are also engaging with regulatory authorities and other stakeholders globally to develop a strategy to resume enrollment as soon as possible.”
Intellia is consulting experts and considering additional risk mitigation measures as it works through the next steps.
The studies going on in the final stages were affected.
Providing an update, Intellia Therapeutics said MAGNITUDE has enrolled more than 650 ATTR-CM patients to date, while 47 ATTR-PN patients have joined MAGNITUDE-2. The company estimates that Nex-Z doses have been administered to more than 450 patients in both trials.
First class one time treatment
Nex-Z uses CRISPR/Cas9 gene editing to permanently disable the TTR gene responsible for producing the toxic transthyretin protein. It is being developed as a potential one-time treatment for both ATTR-CM and ATTR-PN. Earlier clinical data showed a deep and sustained reduction in TTR protein after a single dose.
The therapy has received Orphan Drug status in Europe as well as Orphan Drug and RMAT designation from the US Food and Drug Administration. Intellia is leading the development in collaboration with Regeneron.
Advancing CRISPR-based drugs
Intellia is one of the first companies to incorporate systemic CRISPR gene editing into late-stage clinical trials. The company is focused on developing therapies that address unmet medical needs while expanding delivery and editing platforms for future programs.
